cDNA clones were isolated by immunoscreening a human thyroid carcinoma gt11 expression library with immuniglobulins purified from serum of a patient with autoimmune Graves' disease. One clone (ML8) containing a 1.25 kb insert identified a 2 kb mRNA in human thyroid and thymus tissues and human lumphocytes but not in human brain, pituitary, liver, placenta and thymus epithelium. Using the 650 bp 5' end of the ML8 clone as a probe, a full length 2.05+0.05 kb human cDNA was obtained and sequenced. This cDNA encodes a 69,812 dalton (70kd) protein with two potential N-linked glycosylation sites and a hydrophobic region compatible with a membrane spanning domain. The size of the protein synthesized in vitro from this cDNA using sp6 polymerase and in the baculovirus expression system corresponds to the size deduced from the nucleotide sequence. The protein reacted with sera from several patients with Graves' disease but, not in general, with sera from normal controls. This suggested that the 70 kd protein is a thyroid autoantigen. The functional significance of the transcript in thyroid cells and immune system is currently unknown, but it is of interest that lymphocytes and thyroid are reputed to have TSH binding sites. Studies are underway to determine whether the 70 kd protein is the receptor for TSH and/or an autoantigen involved in the pathogenesis of Graves' disease. Similarly, a cDNA expression library prepared with mRNA from enriched human islets was screened with diabetic patient sera. One of the human clones designated HIDEN 10 contains a 1 kb transcript and encodes a novel protein of 212 amino acids. In addition, several cDNA clones from a rat insulinoma library have been obtained, using a monoclonal anti-islet cell antibody. Partial sequence of these clones indicate that they are novel and are being further analyzed. Our studies should make it possible to use some of these autoantigens in assays for early detection of autoantibodies.